SHOULD GRAVES-DISEASE BE CONSIDERED A COLLAGEN DISORDER OF THE THYROID, SKELETAL-MUSCLE AND CONNECTIVE-TISSUE

Graves' disease comprises hyperthyroidism, ophthalmopathy, pretibial m yxedema and acropachy, which occur separately or in various combinatio ns. We have used the indirect immunofluorescence test to investigate r eactivity of sera from patients with autoimmune thyroid disorders with and without ophthalmopathy, with porcine extra ocular muscle (EOM) an d control tissue substrates. Sera from 75% of patients with Graves' hy perthyroidism (CH) and ophthalmopathy, which we call thy roid-associat ed ophthalmopathy (TAO), contained one or more antibodies reactive wit h EOM compared to 32% of those with GH without the eye disorder, 41% o f patients with Hashimoto's thyroiditis (HT), and 16% of normals. Anti bodies reactive with an EOM connective tissue antigen(s), seen as fluo rescence of the interstitium and endomysium, were found in sera from 1 0% of patients with TAO and 16% of those with GH, but not from any pat ient with HT or normal subject. Similar patterns of connective tissue reactivity were also found in lacrimal gland, skeletal muscle, kidney and salivary gland. Antinuclear antibodies were detected in sera from 31% of patients with TAO, but from only 8% with HT, in no patient with GH and in only 3% of normal subjects. The most common pattern was a f ine speckled fluorescence, found in 45% of sera, consistent with react ivity against the Sm antigen or nuclear RNP. The finding of a high pre valence of ANA and, less often, anti-connective tissue antibodies in p atients with thyroid autoimmunity and ophthalmopathy, is consistent wi th Graves' disease being a ''collagen-like disorder''. The reason why inflammation and resulting tissue damage is limited to the thyroid, co nnective tissue of the skin and orbit, skeletal muscle and, possibly, the lacrimal gland, is unclear. One possibility is cross reaction of A NA with tissue specific membrane proteins in these sites, The extent o f immunologic abnormalities, and the resulting clinical features, in p atients with Graves' disease may reflect the severity of a putative de fect in immune regulation.